Clinical & Genetic Maternal Study in Leber Hereditary Optic Neuropathy

Fighting Blindness has funded research at the Royal Victoria Eye and Ear Hospital, Dublin, into the causes of visual loss in LHON.

In this study, led by Professor Lorraine Cassidy, Dr. Clare Quigley, and Dr. Kirk Stephenson, the researchers investigated both the clinical and genetic nature of LHON beyond which is involved in standard clinical investigation and care. 


Headshot of Dr. Clare Quigley
Dr. Clare Quigley


Headshot of Dr. Kirk Stephenson
Dr. Kirk Stephenson


Project: ‘Clinical & Genetic Maternal Study in Leber Hereditary Optic Neuropathy’

Project Duration: 2021-2022

Amount: €30,000


The Irish Inherited Optic Neuropathy (IION) Study was led by Professor Lorraine Cassidy, Dr. Clare Quigley, and Dr. Kirk Stephenson. This project is now completed and below is the list of publications related to the project:

  • Cardiac conduction abnormalities in Leber Hereditary Optic Neuropathy and asymptomatic maternal relatives. Clare Quigley, Glynis Hanrahan, Kirk Stephenson, Saba Ahmed, Muhammad Mukhtar, Lorraine Cassidy. Eye (Lond). 2023 Mar 6. doi: 10.1038/s41433-023-02466-3. Click here to find the full information about this study.
  • Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups. Clare Quigley, Kirk AJ Stephenson, Paul Kenna, Lorraine Cassidy. Int. J. Mol. Sci. 2023, 24, 1068. Click here to find the full information about this study.
  • The Natural History of Leber’s Hereditary Optic Neuropathy in an Irish Population and Assessment for Prognostic Biomarkers. Stephenson KAJ, McAndrew J, Kenna PF, Cassidy L. Neuro-Ophthalmology. 2022. Click here to find the full information about this study.


LHON is an inherited optic nerve disease which affects 1 in 30,000 – 50,000 people, more commonly men. It causes sudden visual loss, often in both eyes.  The onset is typically in the teens or 20s but may occur at any stage in life. It is caused by mutations in the genetic code of the mitochondria, which are small subunits that reside within the cell.


We spoke to the researchers about the Irish Inherited Optic Neuropathy (IION) Study. Find out more about the study and the personnel who worked in it below:


1. What are the overall aims of the project you are working on, including how it could have an impact on those affected by sight loss?

LHON is caused by variants in the mitochondrial DNA, and is thus transmitted from mother to her children. Up until recently, there were no effective treatment options for visual loss in LHON and visual acuity in the Irish LHON population has been demonstrated at an average of 6/60 (i.e., legal blindness).  An oral medication called Raxone (Idebenone) has been studied in people with LHON and may be beneficial to visual recovery in some patients.

Unaffected relatives of those with LHON who carry the same mitochondrial variant, who do not have vision complaints, may show subclinical eye problems. To investigate this further the researchers recruited people with LHON, or were a first degree maternal relative of a person affected by LHON to the study. These people had detailed eye and heart examinations in addition to detailed ocular imaging tests and genetic testing.


2. Please describe the results from the project

A haplogroup is a set of genetic changes in a large piece of DNA which are passed down within related groups between generations. Genetic testing in the studied LHON families found that asymptomatic relatives relatives (relatives that appear to have no vision loss) with haplogroup H or HV displayed more severe optic neuropathy (visual loss due to optic never damage) than those of other haplogroups.

Optic neuropathy was found to be associated with nerve fibre layer atrophy, more so than with reduced optic nerve head perfusion (blood flow), supporting that loss of nerve tissue is more important in LHON than loss of blood supply to the optic nerve head.

Further work is underway to characterize the blood flow to the optic nerve in relatives of people affected by LHON.

People recruited to the study also had an electrocardiogram (ECG, heart tracing) to assess for arrhythmia (irregular heart rates). Cardiac conduction abnormalities, which have been previously described in LHON, were also found in maternal relatives who had no evidence of optic neuropathy.

In conclusion, this study found that that there may be an asymptomatic group of patient relatives who have clinical signs of optic neuropathy (including visual loss) and other associated signs (such as heart conduction problems) of LHON and that some of this could be explained by differences in genetics.  


3. More about the personnel who worked on the study

Dr Clare Quigley is a graduate of the ophthalmic surgery specialist training program in Ireland. She is currently subspecialising in oculoplastic and orbital surgery in the UK. She is grateful for the support of Fighting Blindness in supporting LHON research, and also for support from Trinity College Dublin via the Eithne Walls Fellowship. Follow Dr Clare Quigley on Twitter at @q_clare to stay informed about her current work.


Dr Kirk Stephenson is a fellow of the Royal College of Surgeons in Ireland in Ophthalmic Surgery.  He has been involved with the Fighting Blindness funded Target 5000 study for which he helped characterise the Irish population with inherited retinal degenerations.  He is currently undertaking fellowship training in Canada in the field of medical and surgical retina and ocular genetics. Follow Dr Kirk Stephenson on Twitter at @KarkStaphonsen to stay informed about his current work.


Dr Paul Kenna is an ocular genetics researcher based at the Research Foundation of the Royal Victoria Eye & Ear Hospital, with an established international reputation for gene discovery and the management of inherited retinal degenerations. Find more about Dr Paul Kenna here. 


Professor Lorraine Cassidy is a Consultant Ophthalmologist, Neuro-ophthalmologist and Oculoplastic surgeon at the Royal Victoria Eye & Ear Hospital.  Her research interests include the diagnosis and management of acquired and inherited optic neuropathies.  She is the sole licensed clinical Irish provider of Raxone (Idebenone), the metabolic treatment for LHON. Find more about Professor Lorraine Cassidy here.


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